How nuclear envelope dynamics can direct laminopathy phenotypes

Abstract

The nuclear envelope separates the genome from the cytoplasmic environment. However, the nuclear envelope is also physically associated with the genome and exerts influence on gene expression and genome modification. The nucleus is dynamic, changing shape and responding to cell movement, disassembling and assembling during cell division, and undergoing rupture and repair. These dynamics can be impacted by genetic disease, leading to a family of diseases called laminopathies. Their disparate phenotypes suggest that multiple processes are affected. We highlight three such processes here, which we believe can be used to classify most of the laminopathies. While much still needs to be learned, some commonalities between these processes, such as proteins involved in nuclear envelope formation and rupture repair, may drive a variety of laminopathies. Here we review the latest information regarding nuclear dynamics and its role in laminopathies related to mutations in the nuclear lamina and linker of nucleoskeleton and cytoskeleton complex (LINC) proteins.